Novel composition for tumor growth control

Abstract

The invention describes a pharmaceutical composition comprising at least compound selected from the group of demethylating agents and HDAC inhibitors and at least one somatostatin analog or dopamine agonist for the treatment of a tumor which expresses a somatostatin and / or dopamine receptor.

Description

[0001]This application is a continuation application filed under 35 U.S.C. §111, claiming priority to U.S. patent application Ser. No. 12 / 225,842 filed Nov. 23, 2009, which is a national stage application filed under 35 U.S.C. §371 of international (PCT) application no. PCT / NL2007 / 050136 filed Apr. 2, 2007, and designating the US, which claims priority to NL patent application number PCT / NL2006 / 000165 filed Mar. 31, 2006.[0002]The invention relates to the field of cancer, more specifically to treatment of tumors, more specifically to the treatment of tumors which express a somatostatin and / or dopamine receptor.[0003]In mammalian cells, approximately 35 to 5% of the cytosine residues in genomic DNA are present as 5-methylcytosine (Ehrlich et al., 1982, Nucl. Acids Res. 10:2709-2721). This modification of cytosine takes place after DNA replication and is catalyzed by DNA methyltransferase using S-adenosyl-methionine as the methyl donor. Approximately 70% to 80% of 5-methylcytosine res...

AI Technical Summary

Benefits of technology

The patent text describes a combination treatment of somatostatin analogs, dopamine agonists, or somatostatin-dopamine chimeric molecules with demethylating agents. This treatment has been found to be more effective in treating tumors that express somatostatin or dopamine receptors. The combination can also target both somatostatin and dopamine receptors simultaneously. The use of a HDAC inhibitor in combination with somatostatin analogs, dopamine agonists, or somatostatin-dopamine chimeric molecules shows promising results in enhancing the therapy.

Problems solved by technology

This is probably caused by intrusion of the 5-methylcytosine into the major groove of the DNA helix, which interferes with the binding of transcription factors.

Secondly, de novo methylation of CpG islands can occur throughout tumor development.

It is possible that the DNA methyltransferase makes mistakes by methylating CpG islands in the nascent strand of DNA without a complementary CpG in the parental strand.

In fact, even in vitro, RNA polymerase II is virtually unable to transcribe nucleosomal DNA under physiological conditions.

Additionally, localized remodeling factors will disrupt nucleosome structure as they act.

For somatostatin analogs regression of growth-hormone producing tumors in the hypophyseal gland has been described (WO 00 / 75186; U.S. Pat. No. 5,538,739), but cessation of treatment, however, often leads to a rapid increase in tumor volume, thus denying a potential growth inhibiting effect.

In general, these undifferentiated tumors with neuroendocrinologic cell differentiation have a poor prognosis at that stage of development; (3) because of the nature of new clinical trials in oncology, often it is mainly those patients who are late in the onset of their disease who are included in the studies.

In addition, there is preliminary evidence that previous chemotherapy might decrease the number of sst; and (iv) it remains unclear whether the sst2-specific analogs applied in clinical trials so far are the best compounds to use.

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